Small Molecules Targeting the Hedgehog Pathway: From Phenotype to Mechanistic Understanding

Since the beginning of 2019, the Hoogendoorn lab is active at the University of Geneva. We are a Chemical Biology lab and our research focuses on the Hedgehog (Hh) signalling pathway and the primary cilium, a small cellular organelle which corrects structure and function, is required to conduct the Hh signal. Ciliary Hh signalling plays an important role in embryonic development, and its dysregulation consequently results in developmental disorders as well as a variety of cancers. We use an interdisciplinary approach, ranging from organic chemistry to cell biology and genetics, to develop chemical tools to study and perturb ciliary signalling. In this account, I will highlight existing small molecules that target the Hh pathway, our efforts to discover new compounds, and the methodologies that we employ for target deconvolution and mechanism of action studies.